Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complex genetic predisposing factors involved. ITGAM and FCγRIIIA are two kinds of immune complex clearance molecules. The variants in ITGAM and FCγRIIIA genes have been confirmed to be associated with SLE. The aim of this study is to investigate the association of mRNA expression levels of ITGAM and FCγRIIIA with SLE. Real-time transcription-polymerase chain reaction analysis (RT-PCR) was used to determine the expression levels of ITGAM and FCγRIIIA mRNA in peripheral blood mononuclear cells (PBMC) from 60 patients with SLE and 60 healthy controls. Flow cytometry was used to measure the expression level of ITGAM and FcγRIIIA from 30 SLE patients and 30 healthy controls. The expression levels of ITGAM mRNA was significantly decreased in SLE patients compared with healthy controls (P = 0.007). Patients with arthritis had higher ITGAM mRNA level than those without arthritis (P = 0.029). The expression level of FCγRIIIA mRNA in SLE patients was significantly lower than that of healthy controls (P = 0.001). Decreased expression level of FCγRIIIA mRNA was also found in patients with LN compared with those without LN (P = 0.015). The level of ITGAM mRNA in patients with anti-SSB positive, anti-RNP positive, complement reduction and increased IgG was significantly reduced. No significant correlation was found between ITGAM and FcγRIIIA mRNA expression level in SLE patients (r = -0.019, P = 0.882). Expression of ITGAM protein in T cells, neutrophil and monocyte of SLE patients was significantly lower than healthy controls (P < 0.05). For FcγRIIIA protein expression in monocyte and NK cells, there were no significant difference between SLE patients and healthy controls (P > 0.05). The altered expression levels of ITGAM and FCγRIIIA mRNA in SLE patients and their correlations with clinical data suggest that ITGAM and FCγRIIIA may play a role in this disease.